Olaparib Maintenance Therapy for Ovarian Cancer

(SOLO-1 Trial)

Not currently recruiting at 211 trial locations

Age: 18+

Sex: Female

Trial Phase: Phase 3

Sponsor: AstraZeneca

Must be taking: Platinum chemotherapy

Disqualifiers: Early stage, Stable disease, Others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 36

Duration: Up to 156 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a medication called Olaparib to determine if it helps women with ovarian cancer who have a specific genetic mutation (BRCA mutation) remain cancer-free longer after their first round of chemotherapy. Participants will take either Olaparib or a placebo (a pill resembling the real medication but without an active ingredient) twice a day. This trial may suit women with advanced ovarian cancer who have a confirmed BRCA mutation and have responded well to initial chemotherapy. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that olaparib is generally well-tolerated as a maintenance treatment for ovarian cancer. One study found that taking olaparib orally at a dose of 400 mg twice daily was manageable for women with recurring ovarian cancer.

However, some serious side effects did occur. About 31% of patients experienced significant adverse reactions, such as high blood pressure. These reactions occurred when olaparib was used with another drug, bevacizumab, so side effects might differ when olaparib is used alone.

Overall, safety data from other studies suggest that olaparib is relatively safe for many patients. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for ovarian cancer?

Researchers are excited about Olaparib for ovarian cancer because it targets cancer cells differently than the standard chemotherapy options. Most treatments for ovarian cancer rely on broad-spectrum chemotherapy, which attacks all rapidly dividing cells. However, Olaparib is a PARP inhibitor, meaning it specifically targets and blocks an enzyme that cancer cells, especially those with BRCA mutations, use to repair their DNA. By inhibiting this repair process, Olaparib helps prevent cancer cells from fixing themselves, potentially leading to better outcomes for patients with these specific genetic profiles.

What evidence suggests that Olaparib might be an effective treatment for ovarian cancer?

Research has shown that Olaparib, which participants in this trial may receive, effectively treats ovarian cancer, particularly in patients with BRCA mutations. In one study, patients taking Olaparib kept their cancer under control longer than those taking a placebo, a pill with no active medicine. The exact duration for cancer control with Olaparib was not reached, but for those on a placebo, it was about 1.2 years. Long-term data also indicate that Olaparib reduces the risk of cancer progression or death. Another review found that Olaparib can significantly extend overall survival. These findings suggest that Olaparib is a promising option for maintaining the health of ovarian cancer patients after initial chemotherapy. ^{6 7 8 9 10}

Who Is on the Research Team?

Kathleen Moore, M.D., MS

Principal Investigator

University of Oklahoma Health Sciences Center, Oklahoma City, USA

Prof Paul DiSilvestro, MD

Principal Investigator

Women & Infants Hospital, Providence, Rhode Island, USA

Are You a Good Fit for This Trial?

This trial is for women with newly diagnosed high-grade ovarian cancer (FIGO stage III-IV) that have specific harmful mutations in BRCA genes. They should have responded well to first-line platinum-based chemotherapy and undergone debulking surgery if needed. Women with stable or worsening disease post-chemotherapy, early-stage cancer, multiple surgeries before the study, or previous chemo for abdominal tumors are excluded.

Inclusion Criteria

I've had surgery aimed at removing as much cancer as possible.

I have a harmful BRCA1 or BRCA2 mutation.

I am a woman with advanced ovarian, peritoneal, or fallopian tube cancer with a BRCA mutation and have finished first-line platinum chemotherapy.

Exclusion Criteria

I have early-stage endometrial cancer and am under 60, or I'm 60+ with a specific early cancer type.

My BRCA1/2 mutations are not harmful.

My cancer did not improve but also did not worsen after my first chemotherapy.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Olaparib or placebo tablets p.o. 300mg twice daily for up to 3 years or until disease progression

Up to 156 weeks

Visits every 12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 weeks

Visits every 24 weeks

Open-label extension (optional)

Participants may continue treatment beyond 2 years if in their best interest

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• Olaparib

Trial Overview The trial tests Olaparib tablets as a maintenance therapy for patients who've had a positive response to initial chemotherapy. It's aimed at preventing cancer from coming back by targeting BRCA mutations which are common in high-grade ovarian cancers.

How Is the Trial Designed?

Group I: Olaparib tablets p.o. 300mg twice daily Experimental Treatment 1 Intervention

Olaparib/placebo tablets p.o 300mg twice daily for up to 3 years or until objective radiological disease progression as per RECIST as assessed by the Investigator. Patients with evidence of stable disease (or those who have progressed), may continue on treatment beyond 2 years, if in the patient's best interest. Dose reduction to 250mg and subsequently 200mg is permitted following confirmation of toxicity

Group II: Placebo tablets p.o. twice daily Placebo Group 1 Intervention

Olaparib/placebo tablets p.o 300mg twice daily for up to 3 years or until objective radiological disease progression as per RECIST as assessed by the Investigator. Patients with evidence of stable disease (or those who have progressed), may continue on treatment beyond 2 years, if in the patient's best interest. Dose reduction to 250mg and subsequently 200mg is permitted following confirmation of toxicity

Who Is Running the Clinical Trial?

AstraZeneca

Lead Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

GOG Foundation

Collaborator

Trials

48

Recruited

18,500+

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Myriad Genetic Laboratories, Inc.

Industry Sponsor

Trials

32

Recruited

14,600+

Published Research Related to This Trial

Olaparib is an effective oral treatment for patients with BRCA mutation-positive ovarian cancer, approved for maintenance therapy after platinum-based chemotherapy, showing good tolerability with common side effects like nausea, fatigue, and anemia being mild to moderate.

Long-term monitoring is recommended due to a low risk of serious hematological complications, such as anemia and myelodysplastic syndrome, ensuring patient safety during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety evaluation of olaparib for treating ovarian cancer. Lheureux, S., Bowering, V., Karakasis, K., et al.[2015]

Olaparib is a powerful inhibitor of PARP-1 and PARP-2, showing effectiveness in treating ovarian cancer, particularly in patients with germline BRCA mutations.

Phase III trials are currently evaluating olaparib's efficacy as a maintenance therapy after initial treatment in patients with BRCA mutations, highlighting its potential role in long-term cancer management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olaparib: an oral PARP-1 and PARP-2 inhibitor with promising activity in ovarian cancer. Gunderson, CC., Moore, KN.[2016]

In a study of 115 relapsing epithelial ovarian cancer patients with BRCA mutations receiving olaparib, the median progression-free survival (PFS) was 12.7 months and overall survival (OS) was 35.4 months after a median follow-up of 21 months.

Key factors associated with longer PFS and OS included a platinum-free interval of 12 months or more, achieving a complete or partial response to treatment, and normalization of CA-125 levels after the last platinum-based chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical factors associated with prolonged response and survival under olaparib as maintenance therapy in BRCA mutated ovarian cancers. Labidi-Galy, SI., de La Motte Rouge, T., Derbel, O., et al.[2022]

Olaparib, a PARP inhibitor, showed a 36% objective response rate in women with relapsed ovarian cancer and a germline BRCA1/2 mutation, even after they had undergone multiple lines of chemotherapy, indicating its efficacy in this challenging patient population.

The median duration of response to olaparib was 7.4 months, and the safety profile was consistent across patients who had received three or more lines of prior chemotherapy, with similar rates of serious adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olaparib monotherapy in patients with advanced relapsed ovarian cancer and a germline BRCA1/2 mutation: a multistudy analysis of response rates and safety. Matulonis, UA., Penson, RT., Domchek, SM., et al.[2022]

Olaparib is particularly effective for patients with BRCA-mutated ovarian cancer, but it also benefits a subset of patients with BRCA wild-type tumors that have loss-of-function mutations in DNA repair genes, showing similar treatment outcomes.

The study suggests that patients with specific HRR gene mutations, even without BRCA mutations, can be identified as a group that may respond well to olaparib, indicating a potential for broader use of this treatment in ovarian cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Candidate biomarkers of PARP inhibitor sensitivity in ovarian cancer beyond the BRCA genes. Hodgson, DR., Dougherty, BA., Lai, Z., et al.[2020]

The OPINION study is evaluating the safety and efficacy of olaparib as a maintenance therapy for women with high-grade serous or endometrioid platinum-sensitive relapsed ovarian cancer who do not have BRCA mutations, involving patients who have undergone at least two prior lines of platinum-based chemotherapy.

The primary goal of the study is to assess progression-free survival, which will help determine how effective olaparib is in delaying cancer progression in this specific patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olaparib maintenance monotherapy in platinum-sensitive, relapsed ovarian cancer without germline BRCA mutations: OPINION Phase IIIb study design. Poveda, AM., Davidson, R., Blakeley, C., et al.[2020]

Olaparib is an effective first-line maintenance treatment for adults with advanced ovarian cancer who have responded to platinum-based chemotherapy, significantly improving progression-free survival compared to placebo in phase III trials.

When combined with bevacizumab, olaparib further enhances treatment efficacy in patients with homologous recombination deficiency (HRD), but does not show benefits in HRD-negative tumors, indicating its targeted effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olaparib: A Review as First-Line Maintenance Therapy in Advanced Ovarian Cancer. Paik, J.[2022]

Citations

1. lynparzahcp.com lynparzahcp.com/ovarian-cancer/efficacy/solo-1.html

LYNPARZA SOLO-1 Trial: Efficacy in Ovarian Cancer Primary analysis. Unprecedented efficacy: Median PFS was not reached with LYNPARZA vs ~1.2 years (13.8 months) with placebo1,5.

2. lynparza.com lynparza.com/ovarian-cancer/results/advanced-ovarian-cancer.html

Results of LYNPARZA: advanced ovarian cancer 168 out of 255 patients on LYNPARZA + bevacizumab did not see their cancer grow or return compared with 40 out of 132 patients on bevacizumab + placebo. 67%.

3. onclive.com onclive.com/view/olaparib-withstands-the-test-of-time-with-long-term-data-supporting-its-role-in-ovarian-cancer-treatment

Olaparib Withstands the Test of Time With Long-Term Data ... The primary outcome was progression-free survival [PFS], and for women randomized to olaparib, the chances of progression or death were reduced ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8921481/

Systematic Review of Olaparib in the Treatment ... The results showed that HR = 1.24 (95%CI = 1.06-1.45, P = 0.006), suggesting that Olaparib can significantly prolong OS in patients with ovarian cancer, as ...

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.22.01549

Overall Survival With Maintenance Olaparib at a 7-Year ... Results indicate a clinically meaningful, albeit not statistically significant, improvement in OS with maintenance olaparib versus placebo, with ...

6. lynparzahcp.com lynparzahcp.com/ovarian-cancer/safety-tolerability/paola-1.html

Adverse Reactions and Tolerability for LYNPARZA® (olaparib ... Serious adverse reactions occurred in 31% of patients who received LYNPARZA + bevacizumab. Serious adverse reactions in >5% of patients included hypertension ( ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/26051946/

Safety evaluation of olaparib for treating ovarian cancer Oral olaparib 400 mg twice daily has acceptable tolerability when administered as maintenance monochemotherapy in women with relapsed OC.

8. lynparza.com lynparza.com/

LYNPARZA® (olaparib) - Official Patient Website Find out about LYNPARZA® (olaparib), a targeted treatment for certain types of cancer. See important safety information, downloadable resources and more.

9. accc-cancer.org accc-cancer.org/docs/ossn-network/industry-news-announcements/solo3-dhcp.pdf?sfvrsn=b70b4ab8_2

solo3-dhcp.pdf Safety data, other than OS, reported for Lynparza in the SOLO3 study were consistent with those reported in other clinical trials with Lynparza. This letter is ...

10. lynparzahcp.com lynparzahcp.com/ovarian-cancer/resource-library.html

LYNPARZA Resource Library for Ovarian Cancer | For HCPs Access LYNPARZA® (olaparib) resource library for ovarian cancer, including clinical guides, patient materials, and prescribing information for HCPs.